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Clinical & Experimental Ophthalmology Jul 2022Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface... (Review)
Review
Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Blindness; Corneal Ulcer; Eye Infections, Fungal; Humans
PubMed: 35610943
DOI: 10.1111/ceo.14113 -
Parasite (Paris, France) 2015Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the... (Review)
Review
Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Adrenal Cortex Hormones; Amebicides; Animals; Biological Assay; Chlorhexidine; Corneal Transplantation; Cross-Linking Reagents; Diagnostic Techniques, Ophthalmological; Host-Parasite Interactions; Humans; Hydroxymercuribenzoates; Mice; Parasitology; Phagocytosis; Protozoan Proteins; Specimen Handling; Virulence
PubMed: 25687209
DOI: 10.1051/parasite/2015010 -
Eye (London, England) Apr 2021Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for... (Review)
Review
Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5-2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.
Topics: Acanthamoeba Keratitis; Anti-Bacterial Agents; Cornea; Drug Resistance, Bacterial; Humans; Risk Factors
PubMed: 33414529
DOI: 10.1038/s41433-020-01339-3 -
Pathogens (Basel, Switzerland) Mar 2021keratitis is an unusual corneal infection that is recently increasing in frequency and is often contracted by contact lens wearers, someone who experienced recent eye... (Review)
Review
keratitis is an unusual corneal infection that is recently increasing in frequency and is often contracted by contact lens wearers, someone who experienced recent eye trauma, or someone exposed to contaminated waters. survive in air, soil, dust, and water. Therefore, eye trauma and poor contact lens hygiene practices lead to the entrapment of debris and thus infection. keratitis results in severe eye pain, inflammation, and defects of the epithelium and stroma that can potentially result in vision loss if not diagnosed early and treated promptly. The disease can be diagnosed using corneal scrape/biopsy, polymerase chain reactions, impression cytology, or in vivo confocal microscopy. Once diagnosed, it is usually treated with an antimicrobial combination therapy of biguanide and aromatic diadine eye drops for several months. Advanced stages of the disease result in vision loss and the need for corneal transplants. Avoiding the risk factors and diagnosing the disease early are the most effective ways to combat keratitis.
PubMed: 33801905
DOI: 10.3390/pathogens10030323 -
Ophthalmology Mar 2024To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK)... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment.
DESIGN
Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895).
PARTICIPANTS
One hundred thirty-five patients treated at 6 European centers.
METHODS
Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes.
MAIN OUTCOME MEASURES
The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates.
RESULTS
One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred.
CONCLUSIONS
PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Acanthamoeba Keratitis; Benzamidines; Biguanides; Orphan Drug Production; Prospective Studies
PubMed: 37802392
DOI: 10.1016/j.ophtha.2023.09.031 -
Pathogens (Basel, Switzerland) May 2022is a free-living amoeba genus able to cause severe infections, such as Granulomatous amoebic encephalitis (GAE), epithelial disorders and a sight-threatening disease...
is a free-living amoeba genus able to cause severe infections, such as Granulomatous amoebic encephalitis (GAE), epithelial disorders and a sight-threatening disease called keratitis (AK) [...].
PubMed: 35631129
DOI: 10.3390/pathogens11050609 -
Diagnostics (Basel, Switzerland) Aug 2023keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is... (Review)
Review
keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is crucial during the management of AK, as delayed diagnosis often results in poor clinical outcomes. Currently, AK diagnosis is primarily achieved through a combination of clinical suspicion, microbiological investigations and corneal imaging. Historically, corneal scraping for microbiological culture has been considered to be the gold standard. Despite its technical ease, accessibility and cost-effectiveness, the long diagnostic turnaround time and variably low sensitivity of microbiological culture limit its use as a sole diagnostic test for AK in clinical practice. In this review, we aim to provide a comprehensive overview of the diagnostic modalities that are currently used to diagnose AK, including microscopy with staining, culture, corneal biopsy, in vivo confocal microscopy, polymerase chain reaction and anterior segment optical coherence tomography. We also highlight emerging techniques, such as next-generation sequencing and artificial intelligence-assisted models, which have the potential to transform the diagnostic landscape of AK.
PubMed: 37627913
DOI: 10.3390/diagnostics13162655 -
Journal of Infection and Public Health Jun 2023Acanthamoeba keratitis is a rare parasitic infection of the cornea that can lead to permanent blindness if not diagnosed and treated promptly. We collected data on the... (Review)
Review
Acanthamoeba keratitis is a rare parasitic infection of the cornea that can lead to permanent blindness if not diagnosed and treated promptly. We collected data on the incidences of Acanthamoeba keratitis from 20 countries and calculated an annual incidence of 23,561 cases, with the lowest rates in Tunisia and Belgium, and the highest in India. We analyzed 3755 Acanthamoeba sequences from the GenBank database across Asia, Europe, North America, South America, and Oceania and genotyped them into T1, T2, T3, T4, T5, T10, T11, T12, and T15. Many genotypes possess different characteristics, yet T4 is the most prevalent genotype. As efficient treatment against Acanthamoeba remains lacking, prevention from early diagnosis via staining, PCR, or in vivo confocal microscopy (IVCM) becomes significant for the condition's prognosis. IVCM is the most recommended approach for the early detection of Acanthamoeba. If IVCM is unavailable, PCR should be used as an alternative.
Topics: Humans; Acanthamoeba Keratitis; Acanthamoeba; Cornea; Genotype; Prognosis
PubMed: 37030037
DOI: 10.1016/j.jiph.2023.03.020 -
Biology Dec 2023Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and... (Review)
Review
Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism's dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms " keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.
PubMed: 38132315
DOI: 10.3390/biology12121489 -
Frontiers in Microbiology 2023is an opportunistic protozoa, which exists widely in nature and is mainly distributed in soil and water. usually exists in two forms, trophozoites and cysts. The... (Review)
Review
is an opportunistic protozoa, which exists widely in nature and is mainly distributed in soil and water. usually exists in two forms, trophozoites and cysts. The trophozoite stage is one of growth and reproduction while the cyst stage is characterized by cellular quiescence, commonly resulting in human infection, and the lack of effective monotherapy after initial infection leads to chronic disease. can infect several human body tissues such as the skin, cornea, conjunctiva, respiratory tract, and reproductive tract, especially when the tissue barriers are damaged. Furthermore, serious infections can cause keratitis, granulomatous amoebic encephalitis, skin, and lung infections. With an increasing number of infections in recent years, the pathogenicity of is becoming more relevant to mainstream clinical care. This review article will describe the etiological characteristics of infection in detail from the aspects of biological characteristic, classification, disease, and pathogenic mechanism in order to provide scientific basis for the diagnosis, treatment, and prevention of infection.
PubMed: 37089530
DOI: 10.3389/fmicb.2023.1147077